Model of the subunit architecture of eukaryotic vacuolar ATPase.
(A) V1-ATPase (top) and membrane bound Vo proton channel (bottom) are linked by three peripheral stalks (EG1, EG2, EG3) that connect the top of the V1 to subunits C, H, and the N-terminal domain of the membrane integral subunit a (aNT). Subunits C, H and aNT are two domain proteins with Chead and Cfoot, HNT and HCT, aNT(proximal) and aNT(distal) domains, respectively. (B) During enzyme regulation by reversible dissociation, V1-ATPase is released from the membrane bound Vo and the activity of both resulting complexes is silenced. To enable enzyme disassembly, protein-protein interactions involving subunits EG, C, H, DF, d and aNT have to be broken.